1. Field
Disclosed herein are methods for selectively producing crystal polymorphs of the compound 1-((6-Chloro-3-pyridinyl)methyl)-N-nitro-imidazolidinimine, also known as imidacloprid.
2. Description of Related Art
Solid exist in either amorphous or crystalline forms. In the case of crystalline forms, molecules are positioned in 3-dimensional lattice sites. Crystallization of solids from solution is known in the art, for example by mixing the desired compound in an appropriate amount of solvent or mixture of solvents, heating to achieve dissolution, and cooling to precipitate the product. Alternatively, the compound can be dissolved in one solvent, and a second solvent is added, until precipitation is achieved. Also, the reaction can be seeded with the appropriate compound in order to induce crystallization, as known in the art.
When a compound recrystallizes from a solution or slurry, it may crystallize with different spatial lattice arrangements, a property referred to as “polymorphism”, with the different crystal forms individually being referred to as a “polymorph”. Different polymorphic forms of a given substance may also differ from each other with respect to one or more physical properties, such as solubility, true density, crystal shape, compaction behavior, flow properties, and/or solid state stability.
In the case of a chemical substance that exists in two (or more) polymorphic forms having different thermodynamic stabilities, the more unstable forms generally convert to the more thermodynamically stable forms at a given temperature after a sufficient period of time. When this transformation is not rapid, the thermodynamically unstable form is referred to as the “metastable” form. In general, the stable form exhibits the highest melting point, the lowest solubility, and the maximum chemical stability of the different polymorphic forms. However, the metastable form may exhibit sufficient chemical and physical stability under normal storage conditions to permit its use in a commercial form. Furthermore, the metastable form, although less stable than the most thermodynamically stable polymorphic form, may exhibit properties that are more desirable than those of the more stable form, such as better formulative ability, improved dispersability in water, and the like.
It has been discovered that the compound imidacloprid exists in two polymorphic forms: a thermodynamically stable form, known as Form I, and a metastable form, known as Form II. The powder XRD patterns and data for the two polymorphic forms are also distinctly different. Form I exhibits an X-ray powder diffraction pattern substantially as given in Table 1, having characteristic peaks (expressed in degrees 2θ (+/−0.2°θ) at one or more of the following positions: 9.560, 16.040, 19.220, 19.720, 23.560, 24.440, 25.740, 29.020 and 29.100.
TABLE 12θd-valueI/I09.2809.522029.5609.24372011.9007.4308213.1406.7322213.8206.4025214.0006.3205214.4006.1459215.4205.7415215.9805.5416616.0405.5210816.9805.2174217.0605.1931318.4804.7972419.2204.614110019.6604.5118519.7204.4982721.1604.1952521.3004.1680423.0003.8636323.0803.8504323.2003.8308423.4403.7921423.5603.7730723.9803.7079224.4403.6391724.9603.5645225.3603.5092225.7403.45821127.2803.2664228.0603.1773428.1803.1641228.8203.0953229.0203.07441729.1003.06611029.6203.0134229.7203.0035630.2402.95312
Form I of imidacloprid also exhibits a differential Scanning calorimetry (DSC) thermogram substantially as shown in FIG. 1. This thermogram is characterized by a predominant endotherm peak at about 145.7° C., as measured by Differential Scanning calorimeter at a scan rate of 10° C. per minute.
Form II of imidacloprid exhibits an X-ray powder diffraction pattern substantially as indicated in Table 2, having characteristic peaks (expressed in degrees 2θ (+/−0.2°θ) at one or more of the following positions: 4.580, 13.780, 15.000, 18.220, 18.420, 18.880 and 23.120.
TABLE 22θd-valueI/I04.58019.277699.1609.646519.3209.4815113.5206.5438113.7806.42102914.8005.9806215.0005.9014716.2605.4468116.4405.3875418.2204.8650618.4204.812610018.7604.7262318.8804.6964621.2204.1835022.0804.0225222.1604.0081122.8403.8903123.1203.8438723.3003.8145123.6203.7636226.1803.4011226.2803.3884129.5403.0214229.6203.0134229.9602.9800330.0402.97233
Form II also exhibits a Differential Scanning calorimetry (DSC) thermogram substantially as shown in FIG. 2, which is characterized by a predominant endotherm peak at about 136.5° C., as measured by Differential Scanning calorimeter at a scan rate of 10° C. per minute.
A mixture of Form I and Form II of Imidacloprid also exhibits a Differential Scanning calorimetry (DSC) thermogram substantially as shown in FIG. 3, which is characterized by two predominant endotherm peaks at about 138.2° C. and 145.7° C., as measured by Differential Scanning calorimeter at a scan rate of 10° C. per minute.
Useful formulations of compounds containing both Form I and Form II can be prepared in conventional ways. These include preparation as dusts, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, and the like. In particular, the compound containing both Form I and Form II may be formulated as solutions and suspensions. The inventor found that compared to Form I, Form II is easier to formulate into liquid formulations, like solutions, suspensions, emulsions and emulsifiable concentrate. While both forms can be difficult to formulate into agrochemically acceptable formulation, imidacloprid in Form I is especially difficult to formulate into liquid formulations because of gel formation.
During the manufacturing process, Form I is more readily made when imidacloprid is recrystallised in aqueous solution. Because Form I is so difficult to formulate into agrochemically acceptable formulations, if the Form I material obtained during recrystallisation cannot be converted to Form II, then it must be disposed of, resulting in lost revenue and inefficient production processes.
To date, there are no simple methods for controlling the crystallization of polymorphic forms of imidacloprid. There is thus an urgent and unmet need in the art for efficient method for selectively controlling the crystallization of polymorphic forms of imidacloprid.